hexyl 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑四嗪类
• 英文名称: hexyl 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate
• 英文别名: n-hexyl 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxylate；hexyl 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxylate；Hexyl 3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate
• 化学式: C₁₂H₁₇N₅O₃
• 分子量: 279.299
• InChiKey: OIMDZKSIZPZGLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  替莫唑胺 在 氯化亚砜 、 硫酸 、 N,N-二甲基甲酰胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 22.0h， 生成 hexyl 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate
  参考文献：
  名称：

  A novel series of phenolic temozolomide (TMZ) esters with 4 to 5-fold increased potency, compared to TMZ, against glioma cells irrespective of MGMT expression

  摘要：

  诊断为多形性胶质母细胞瘤（GBM）的患者的标准治疗是替莫唑胺（TMZ）。

  DOI：

  10.1039/d0ra02686g

文献信息

• Synthesis of temozolomide esters as potent anticancer pro-drugs for topical and transdermal applications in treatments of cancers
  申请人：Wang Yongfeng

  公开号：US20060047117A1

  公开（公告）日：2006-03-02

  This invention relates to the use of temozolomide esters (4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxylate esters) Formula 1 as potent anticancer pro-drugs for treatment of cancers by topical and transdermal applications, and to a novel process for synthesis of temozolomide esters by a direct esterification of temozolomide acid (3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxylic acid) with a halogeno-aliphatic compound in presence of a base, or with an alcohol in presence of a dehydrate agent.

  该发明涉及使用替莫唑胺酯（4-二氢-3-甲基-4-氧基咪唑[5,1-d]-1,2,3,5-四唑-8-羧酸酯）化合物（式1）作为有效的抗癌前药，用于局部和经皮应用治疗癌症，并涉及一种新型合成替莫唑胺酯的方法，即通过直接酯化替莫唑胺酸（3,4-二氢-3-甲基-4-氧基咪唑[5,1-d]-1,2,3,5-四唑-8-羧酸）与卤代脂肪化合物在碱的存在下，或与醇在脱水剂存在下进行酯化。
• [EN] TEMOZOLOMIDE ANALOGS AND METHODS OF USE<br/>[FR] ANALOGUES DE TÉMOZOLOMIDE ET PROCÉDÉS D'UTILISATION
  申请人：ST JOHNS CANCER INST

  公开号：WO2022026756A1

  公开（公告）日：2022-02-03

  Disclosed herein are compounds and methods for treating cancer, such as glioblastomas.

  本文揭示了用于治疗癌症（如胶质母细胞瘤）的化合物和方法。
• A novel series of phenolic temozolomide (TMZ) esters with 4 to 5-fold increased potency, compared to TMZ, against glioma cells irrespective of MGMT expression
  作者：Leroy Shervington、Oliver Ingham、Amal Shervington

  DOI：10.1039/d0ra02686g

  日期：——

  The standard of care treatment for patients diagnosed with glioblastoma multiforme (GBM) is temozolomide (TMZ).

  诊断为多形性胶质母细胞瘤（GBM）的患者的标准治疗是替莫唑胺（TMZ）。
• Pharmaceutical Composition Comprising Temozolomide Ester
  申请人：Wang Yongfeng

  公开号：US20080044457A1

  公开（公告）日：2008-02-21

  The present invention discloses general formula I of Temozolomide-8-carboxylate compounds, the process for preparation, pharmaceutical compositions comprising the compounds and the use of the compounds and pharmaceutical compositions for the manufacture of an antitumor medicament. The said pharmaceutical composition comprises one or more general formula I Temozolomide-8-carboxylate compounds as active ingredient, together with conventional pharmaceutical carriers. The composition also comprises one or more pharmaceutically acceptable acidic material, optionally second or tertiary alcohol or ester or ether derivatives thereof. The said pharmaceutical composition can be made into various common formulations, particularly oral formulations as well as topically transdermal patches. The present invention also discloses the application of the compounds and the compositions to treat tumor.

  本发明公开了特莫唑酰胺-8-羧酸酯化合物的通用式I，其制备过程，包含该化合物的制药组合物以及用于制造抗肿瘤药物的化合物和制药组合物的用途。所述制药组合物包括一种或多种通用式I特莫唑酰胺-8-羧酸酯化合物作为活性成分，以及常规的制药载体。该组合物还包括一种或多种药学上可接受的酸性物质，可选的第二或第三醇或酯或醚衍生物。该制药组合物可以制成各种常见的配方，特别是口服制剂以及局部透皮贴片。本发明还公开了该化合物和组合物用于治疗肿瘤的应用。
• PHARMACEUTICAL COMPOSITION COMPRISING TEMOZOLOMIDE ESTER
  申请人：Tianjin Tasly Group Co., Ltd.

  公开号：EP1798234A1

  公开（公告）日：2007-06-20

  The present invention discloses general formula I of Temozolomide-8-carboxylate compounds, the process for preparation, pharmaceutical compositions comprising the compounds and the use of the compounds and pharmaceutical compositions for the manufacture of an antitumor medicament. The said pharmaceutical composition comprises one or more general formula I Temozolomide-8-carboxylate compounds as active ingredient, together with conventional pharmaceutical carriers. The composition also comprises one or more pharmaceutically acceptable acidic material, optionally second or tertiary alcohol or ester or ether derivatives thereof. The said pharmaceutical composition can be made into various common formulations, particularly oral formulations as well as topically transdermal patches. The present invention also discloses the application of the compounds and the compositions to treat tumor.

  本发明公开了通式 I 替莫唑胺-8-羧酸盐化合物、制备工艺、包含该化合物的药物组合物以及使用该化合物和药物组合物制造抗肿瘤药物。所述药物组合物包含一种或多种作为活性成分的通式 I 替莫唑胺-8-羧酸盐化合物，以及常规药物载体。该组合物还包括一种或多种药学上可接受的酸性物质，可选择第二或第三醇或其酯或醚衍生物。所述药物组合物可制成各种常见制剂，特别是口服制剂以及局部透皮贴剂。本发明还公开了化合物和组合物治疗肿瘤的应用。